Lymphoid cells from patients with chronic lymphocytic leukemia (CLL) of B cell origin, from healthy volunteers, and four established cell lines (three immunoglobulin-producing and one "null" cell) were stimulated in vitro by cyclic nucleotides (cAMP, dibutyryl cAMP, cGMP, and 8-Br cGMP), pokeweed mitogen (PWM), and by dithiothreitol (DTT). PWM stimulated polyclonal immunoglobulin production in vitro in normal lymphocytes, but not in neoplastic cells from CLL. Exogenous cAMP and phosphodiesterase inhibitors (theophylline and aminophylline) occasionally produced a small increase in immunoglobulin-secreting cells from normal donors and in established B cell lines in 24-72 hour cultures. However, the results were not reproducible, and no dose-related response was observed. Cytoplasmic immunoglobulin was never detected in 1-4 day cultures of CLL cells containing cAMP and/or phosphodiesterase inhibitors. No significant increase in immunoglobulin-containing cells was obtained by applying DTT in short-term lymphocyte cultures from healthy donors. Cytochalasin B, which might be expected to produce dissociation of synthesis and secretion through its action on microfilaments, did not produce significant increase of lymphocytes with cytoplasmic immunoglobulins. The ionophore A23187 stimulated blast transformation and immunoglobulin production by normal B lymphocytes. A23187 mainly stimulated IgM production which started at 48 hours and generally reached a peak at 96 hours. Studies are in progress to determine the mechanism involved. BIBLIOGRAPHIC REFERENCES: Kersey, J.H. and Gajl-Peczalska, K.J.: T and B lymphocytes in humans. A review. Am. J. Path. 81: 446-458, 1975. Gajl-Peczalska, K.J., Chartrand, S., and Kersey, J.H.: Ionophore A23187 stimulation of human B and T lymphocyte proliferation. Fed. Proc. 35: 822, 1976 (Abstr.).